Pathogenesis
Pathogenesis
Radicular granuloma formation is a classic Type IV (delayed-type) hypersensitivity response. Persistent antigen stimulation drives macrophage accumulation and epithelioid transformation. Lymphocytes, plasma cells, and fibroblasts proliferate; new blood vessels form (angiogenesis); and the lesion becomes encapsulated in fibrous tissue.
Epithelial cells resting in the periodontal ligament (Malassez cell rests — remnants of Hertwig's root sheath) are stimulated to proliferate by growth factors from activated macrophages (EGF, PDGF, IL-1α). This epithelial proliferation may remain as cords and strands (periapical granuloma with epithelium) or cavitate and fill with fluid under osmotic pressure to form a radicular cyst.
The cyst lumen fills with transudate, necrotic cells, cholesterol crystals (from lysed erythrocytes and inflammatory cells), and sometimes pus. Elevated osmotic pressure drives further fluid accumulation, and the cyst expands by bone resorption driven by prostaglandins and cytokines from the cyst lining.
Bone resorption at the periphery of the lesion is mediated by RANKL from T cells and fibroblasts activating osteoclasts. Osteoblastic bone formation occurs at the periphery, explaining the variable radiographic appearance: diffuse radiolucency (granuloma) vs. well-defined radiolucency with corticated margin (cyst).